title: Serodiagnostic assays for celiac disease based on the open or closed conformation of the autoantigen, transglutaminase 2.
abstract: The autoantigen of celiac disease, transglutaminase 2 (TG2), adopts an open conformation during enzymatic activation. We studied diagnostic accuracy of serodiagnostic assays using TG2 in its open and closed conformation as antigens in patients with diagnostic difficulties. The open TG2 antibody (TG2ab) test identified 93% of untreated celiac patients in contrast to 44%, 27%, and 68% detected by closed and conventional TG2ab and endomysial antibody (EmA) tests, respectively. The assay was able to detect 60% of non-responding celiac patients seronegative for conventional TG2ab and EmA. The titers of the open TG2abs were higher than those of the closed TG2abs. The serological test utilizing TG2 in an open conformation was more accurate than the other assays in finding active celiac disease even in patients having negative or borderline conventional celiac autoantibodies and in revealing poor dietary response non-invasively. It thus offers a promising tool in the diagnostics and follow-up of celiac disease.
authors.affiliation: Pediatric Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Lindfors
authors.forename: Outi
authors.initials: O
authors.lastname: Koskinen
authors.forename: Kalle
authors.initials: K
authors.lastname: Kurppa
authors.forename: Kaija
authors.initials: K
authors.lastname: Laurila
authors.forename: Pekka
authors.initials: P
authors.lastname: Collin
authors.forename: Katri
authors.initials: K
authors.lastname: Haimila
authors.forename: Jukka
authors.initials: J
authors.lastname: Partanen
authors.forename: Päivi
authors.initials: P
authors.lastname: Saavalainen
authors.forename: Markku
authors.initials: M
authors.lastname: Mäki
authors.forename: Katri
authors.initials: K
authors.lastname: Kaukinen
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology; D002446:Celiac Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis* / Q000276:immunology; D008297:Male; D011487:Protein Conformation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012372:ROC Curve; D012698:Serologic Tests / Q000379:methods; D011503:Transglutaminases / Q000737:chemistry* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007070:Immunoglobulin A; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins